Alzheimer's disease Advax CpG-adjuvanted MultiTEP-based dual and single vaccines induce high-titer antibodies against various forms of tau and Aβ pathological molecules

Hayk Davtyan, Karen Zagorski, Harinda Rajapaksha, Armine Hovakimyan, Arpine Davtyan, Irina Petrushina, Konstantin Kazarian, David Cribbs, Nikolai Petrovsky, Michael Agadjanyan, Anahit Ghochikyan

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Abstract

Although β-amyloid (Aβ) may be the primary driver of Alzheimer's disease (AD) pathology, accumulation of pathological tau correlates with dementia in AD patients. Thus, the prevention/inhibition of AD may require vaccine/s targeting Aβ and tau simultaneously or sequentially. Since high antibody titers are required for AD vaccine efficacy, we have decided to generate vaccines, targeting Aβ (AV-1959R), Tau (AV-1980R) or Aβ/tau (AV-1953R) B cell epitopes, based on immunogenic MultiTEP platform and evaluate the immunogenicity of these vaccines formulated with Advax CpG, delta inulin, Alhydrogel ®, Montanide-ISA51, Montanide-ISA720, MPLA-SM pharmaceutical grade adjuvants. Formulation of AV-1959R in Advax CpG induced the highest cellular and humoral immune responses in mice. The dual-epitope vaccine, AV-1953R, or the combination of AV-1959R and AV-1980R vaccines formulated with Advax CpG induced robust antibody responses against various forms of both, Aβ and tau pathological molecules. While anti-Aβ antibody titers after AV-1953R immunization were similar to that in mice vaccinated with AV-1959R or AV-1959R/AV-1980R combination, anti-tau titers were significantly lower after AV-1953R injection when compared to the AV-1980R or AV-1959R/AV-1980R. In silico 3D-modeling provided insight into the differences in immunogenicity of these vaccine constructs. In sum, AV-1959R and AV-1980R formulated with Advax CpG adjuvant were identified as promising immunogenic vaccines for ongoing pre-clinical assessment and future human clinical trials.

Original languageEnglish
Article number28912
Number of pages13
JournalScientific Reports
Volume6
DOIs
Publication statusPublished - 1 Jul 2016

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    Davtyan, H., Zagorski, K., Rajapaksha, H., Hovakimyan, A., Davtyan, A., Petrushina, I., Kazarian, K., Cribbs, D., Petrovsky, N., Agadjanyan, M., & Ghochikyan, A. (2016). Alzheimer's disease Advax CpG-adjuvanted MultiTEP-based dual and single vaccines induce high-titer antibodies against various forms of tau and Aβ pathological molecules. Scientific Reports, 6, [28912]. https://doi.org/10.1038/srep28912